2.1 Field of the Invention
The present invention relates to the field of anti-viral borinic acid ester compounds and uses thereof as well as preparing and using these compounds, and pharmaceutical compositions thereof.
2.2 The Related Art
One hallmark of the modem era of medicine has been the decline in morbidity and mortality associated with bacterial and fungal infections. However, similar successes against various viral infections have not been matched.
Viruses are implicated in a variety of animal and human disease. Numerous approaches have been proposed to combat these pathogens which include, but are not limited to, herpesviruses 1 and 2 (HSV-1 and HSV-2), influenza viruses A, B and C (orthomyxoviruses), parainfluenza viruses 1-4, syncytial virus, Epstein Barr virus, rhinoviruses, human immunodeficiency viruses (HIV), polioviruses, coxsackie viruses, echoviruses, rubella virus, varicella-zoster virus, neurodermatrophic virus, variola virus, cytomegalovirus, hepatitis A, B and C viruses, papoviruses, rabies virus, yellow fever virus, dengue virus, West Nile virus and severe acute respiratory syndrome (SARS) virus. Table 1 illustrates various viruses and their associated human diseases.
One approach in the development of anti-viral compounds has been to identify compounds which interfere with the normal viral metabolism and replication in infected host cells. During the screening of new borinic ester compounds, we have found that certain of these compounds show anti-viral activity in cell culture assay systems.
TABLE 1Virus CategoryPertinent Human DiseasesRNA VirusesPicornaviridaePolioHuman hepatitis AHuman rhinovirusTogavindae andRubella (German measles)FlaviviridaeYellow feverCoronavindaeHuman respiratory coronavirus (HCY)Severe acute respiratory syndrome (SAM)RhabdovindaeLyssavirus - RabiesParamyxoviridaeParamyxovirus - MumpsMorbillvirus - MeaslesPneumovirus - Respiratory syncytial virusOrthomyxoviridaeInfluenzaBunyaviridaeBunyavirus - Bunyamwera (BUN)Hantavirus - Hantaan (HTN)Nairevirus - Crimean-Congo hemorrhagicfever (CCHF)Phlebovinis- Sandfly fever (SFN)Uukuvirus - Uukuniemi (UUK)Rift Valley Fever- (RVFN)ArenaviridaeJunin - Argentine hemorrhagic feverMachupo - Bolivian hemorrhagic feverLassa - Lassa feverLCM- aseptic lymphocyctic chodomeningitisReoviridaeRotovirusReovirusOrbivirusRetroviridaeHuman immunodeficiency virus 1 (HIV-1)Human immunodeficiency virus 2 (HIV-2)Simian immunodeficiency virus (SIV)DNA VirusesPapovaviridaePediatric viruses that reside in kidneyAdenoviridaeHuman respiratory distress and somedeep-seated eye infectionsPaivoviddaeHuman gastrointestinal distress(Norwalk Virus)HerpesviridaeHerpes simplex virus 1 (HSV-1)Herpes simplex virus 2 (HSV-2)Human cytomegalovirus (HCMV)Variceila zoster virus (VZV)Epstein-Sam virus (EBV)Human herpes virus 6 (HHV6)PoxyiridaeOrthopoxyirus is sub-genus for smallpoxHepadnaviddaeHepatitis B virus (HBV)Hepatitis C virus (HCY)
Many existing compounds currently in use for treating viral diseases are subject to resistance mechanisms, are expensive to make, do not adequately treat patients or have adverse side effects. Therefore, there is a continuing need for new compounds which act to kill viruses, to inhibit viral replication or to block the pathogenic action of viruses.
Thus, there continues to be a need in the medical arts for novel, more effective, anti-viral compounds, especially for treating infections that are either intrinsically poorly responsive or resistant to currently available therapies.